Are Mutation Carrier Patients Different from Non-Carrier Patients? Genetic, Pathology, and US Features of Patients with Breast Cancer.

Abstract

Simple SummaryUp to 30% of breast cancer patients are carriers of pathogenic mutations in breast cancer susceptibility genes. Except for BRCA1/2 genes that account only for 22–30% of hereditary breast cancer, less is known about the remaining genes that are prone to breast cancer. Our aim was to retrospectively evaluate the relationship between the pathogenic mutations (BRCA and non-BRCA), US features, and histopathologic findings of breast cancer patients with and without mutations. We concluded that carrier patients (BRCA, TP53, PALB, CHEK, ATM, RAD) seem to exhibit benign imaging findings on US compared to mutation-negative patients. Furthermore, carrier patients had the majority of tumors with higher histologic grade and a higher proliferation index. BRCA1, TP53, and RAD carriers accounted for up to one third of the ER-negative tumors from the mutation group. Axillary US performed worse in depicting axillary metastatic lymph nodes in carrier patients, compared to negative patients.The purpose of this study is to evaluate the relationship between the pathogenic/likely pathogenic mutations, US features, and histopathologic findings of breast cancer in mutation carriers compared to non-carrier patients. Methods: In this retrospective study, we identified 264 patients with breast cancer and multigene panel testing admitted to our clinic from January 2018 to December 2020. Patient data US findings, US assessment of the axilla, multigene panel tests, histopathology, and immunochemistry reports were reviewed according to the BI-RADS lexicon. Results: The study population was comprised of 40% pathogenic mutation carriers (BRCA1, BRCA2, CHEK2, ATM, PALB, TP 53, NBN, MSH, BRIP 1 genes) and 60% mutation-negative patients. The mean patient age was 43.5 years in the carrier group and 44 years in the negative group. Carrier patients developed breast cancer with benign morphology (acoustic enhancement, soft elastography appearance) compared to non-carriers (p < 0.05). A tendency towards specific US features was observed for each mutation. BRCA1 carriers were associated with BC with microlobulated margins, hyperechoic rim, and soft elastography appearance (p < 0.05). Estrogen receptor (ER)-negative tumors were associated with BRCA1, TP53, and RAD mutations, while BRCA2 and CHEK2 were associated with ER-positive tumors. Conclusions: Patients with pathogenic mutations may exhibit BC with benign US features compared to negative, non-carrier patients. BRCA1, TP53, and RAD carriers account for up to one third of the ER tumors from the carrier group. Axillary US performed worse in depicting involved lymph nodes in carrier patients, compared to negative patients.